The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake
Open accessAbstract
How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin. Calorie intake regulates mTORC1 in Paneth cells, but not ISCs, and forced activation of mTORC1 in Paneth cells during calorie restriction abolishes the ISC-augmenting effects of the niche. Finally, increased expression of bone stromal antigen 1 (Bst1) in Paneth cells—an ectoenzyme that produces the paracrine factor cyclic ADP ribose—mediates the effects of calorie restriction and rapamycin on ISC function. Our findings establish that mTORC1 non-cell-autonomously regulates stem-cell self-renewal, and highlight a significant role of the mammalian intestinal niche in coupling stem-cell function to organismal physiology.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“DR increases intestinal and muscle stem functions through cell-extrinsic mechanisms”
From The Hallmarks of Aging (2013) · cites this paper as Yilmaz et al., 2012
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“mTORC1 inhibition with rapamycin, which can postpone aging by improving proteostasis (see section on Loss of Proteostasis) and by affecting energy sensing (see section on Deregulated Nutrient-sensing), may also improve stem cell function in the epidermis, in the hematopoietic system, and in the intestine”
From The Hallmarks of Aging (2013) · cites this paper as Yilmaz et al., 2012
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Rapamycin also increases the self-renewal capacity of mouse intestinal stem cells, via a non-cell autonomous mechanism mediated by inhibition of mTORC1 in the adjacent Paneth cells 96.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [96]
In the citing paper
“mTOR, a potent activator of protein translation and inhibitor of autophagy, has been shown to regulate the self-renewal and differentiation of HSCs and intestinal stem cells79,80.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [79]
In the citing paper
“CR can also enhance or maintain stem cell function during aging by increasing the expression of brain-derived neurotrophic factor in the brain and reducing the mTOR complex 1 (mTORC1) pathway in intestine79,112.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [79]
In the citing paper
“CR can also enhance or maintain stem cell function during aging by increasing the expression of brain-derived neurotrophic factor in the brain and reducing the mTOR complex 1 (mTORC1) pathway in intestine79,112.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [79]
In the citing paper
“Paneth cells, found in close association with intestinal stem cells in humans and mice, are an important source of niche factors, including epidermal growth factor, Wnt3A and Notch ligand79,156, although the effect of aging on their activity is yet to be elucidated.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [79]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
Identification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Sato, T., van Es, J. H., Snippert, H. J., Stange, D. E., Vries, R. G., van den Born, M., Barker, N., Shroyer, N. F., van de Wetering, M., & Clevers, H. (2011) · Nature · doi:10.1038/nature09637 · Cited by 2,510
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,365
Self-citationSnippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.016 · Cited by 1,951
Bmi1 is expressed in vivo in intestinal stem cells
Sangiorgi, E., & Capecchi, M. R. (2008) · Nature Genetics · doi:10.1038/ng.165 · Cited by 1,245
Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells
Yilmaz, Ö. H., Valdez, R., Theisen, B. K., Guo, W., Ferguson, D. O., Wu, H., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature04703 · Cited by 1,113
Self-citationTranscription Factor Achaete Scute-Like 2 Controls Intestinal Stem Cell Fate
van der Flier, L. G., van Gijn, M. E., Hatzis, P., Kujala, P., Haegebarth, A., Stange, D. E., Begthel, H., van den Born, M., Guryev, V., Oving, I. M., et al. (2009) · Cell · doi:10.1016/j.cell.2009.01.031 · Cited by 752
Interconversion Between Intestinal Stem Cell Populations in Distinct Niches
Takeda, N., Jain, R., LeBoeuf, M. R., Wang, Q., Lu, M. M., & Epstein, J. A. (2011) · Science · doi:10.1126/science.1213214 · Cited by 742
Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation
Zhu, L., Gibson, P., Currle, D. S., Tong, Y., Richardson, R. J., Bayazitov, I. T., Poppleton, H., Zakharenko, S. S., Ellison, D. W., & Gilbertson, R. J. (2008) · Nature · doi:10.1038/nature07589 · Cited by 690
Cited by
Sorted by citations
Items 301–400 of 751
Calorie restriction prevents age-related changes in the intestinal microbiota
Kurup, K., Matyi, S., Giles, C. B., Wren, J. D., Jones, K. L., Ericsson, A. C., Raftery, D., Wang, L., Promislow, D., Richardson, A. G., et al. (2021) · Aging · doi:10.18632/aging.202753 · Cited by 35
It is not all about regeneration: Planarians striking power to stand starvation
Felix, D. A., Gutiérrez‐Gutiérrez, Ó., Espada, L., Thems, A., & González‐Estévez, C. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.04.010 · Cited by 43
Caloric restriction maintains stem cells through niche and regulates stem cell aging
Maharajan, N., Vijayakumar, K. A., Jang, C. H., & Cho, G. (2019) · Journal of Molecular Medicine · doi:10.1007/s00109-019-01846-1 · Cited by 38
An efficient intestinal organoid system of direct sorting to evaluate stem cell competition in vitro
Fujimichi, Y., Otsuka, K., Tomita, M., & Iwasaki, T. (2019) · Scientific Reports · doi:10.1038/s41598-019-55824-1 · Cited by 38
Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases
Laulajainen‐Hongisto, A., Toppila-Salmi, S. K., Luukkainen, A. T., & Kern, R. C. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00204 · Cited by 40
Hou, Q., Dong, Y., Yu, Q., Wang, B., Shen, L., Guo, Y., & Zhang, B. (2020) · The FASEB Journal · doi:10.1096/fj.201902573rr · Cited by 39
Kim, T., Kim, S., Kim, Y., Lee, Y., Lee, S., Lee, S.-H., & Kweon, M. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.12.015 · Cited by 39
Hormonal Control of Stem Cell Systems
Gancz, D., & Gilboa, L. (2013) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101512-122331 · Cited by 37
Shuttling of information between the mucosal and luminal environment drives intestinal homeostasis
Asselin, C., & Gendron, F. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.02.049 · Cited by 37
Iglesias, M., Felix, D. A., Gutiérrez‐Gutiérrez, Ó., Miguel-Bonet, M. D. M. D., Sahu, S., Fernández-Varas, B., Perona, R., Aboobaker, A. A., Flores, I., & González‐Estévez, C. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.06.005 · Cited by 39
Joly, A., & Rousset, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176362 · Cited by 39
Yang, J., Zhao, X., Patel, A., Potru, R., Azizi-Ghannad, S., Dolinger, M. T., Cao, J. H., Bartholomew, C., Mazurkiewicz, J. E., Conti, D., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.03.046 · Cited by 37
Dietary interventions as regulators of stem cell behavior in homeostasis and diseasePreprint
Novak, J. S. S., Baksh, S. C., & Fuchs, E. V. (2021) · Genes & Development · doi:10.1101/gad.346973.120 · Cited by 38
Tissue Homeostasis and Non-Homeostasis: From Cell Life Cycles to Organ States
O’Brien, L. E. (2022) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-120420-114855 · Cited by 42
Purdel, C. N., Margina, D. M., Adam-Dima, I., & Ungurianu, A. (2023) · Nutrients · doi:10.3390/nu15235005 · Cited by 37
Concise Review: The Potential Use of Intestinal Stem Cells to Treat Patients with Intestinal Failure
Hong, S. N., Dunn, J., Stelzner, M. G., & Martı́n, M. G. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2016-0153 · Cited by 36
Barron, L. M., Sun, R. C., Aladegbami, B. G., Erwin, C. R., Warner, B. W., & Guo, J. (2016) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.10.006 · Cited by 36
Feng, Y., Demehri, F. R., Xiao, W., Tsai, Y.-H., Jones, J. C., Brindley, C. D., Threadgill, D. W., Holst, J. J., Hartmann, B., Barrett, T. A., et al. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.12.005 · Cited by 35
Sato, T., Ishikawa, S., Asano, J., Yamamoto, H., Fujii, M., Sato, T., Yamamoto, K., Kitagaki, K., Akashi, T., Okamoto, R., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0545-5 · Cited by 36
The role of stem cell niche in intestinal aging
Pentinmikko, N., & Katajisto, P. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111330 · Cited by 39
Self-citationTorrens‐Mas, M., Perelló-Reus, C. M., Navas-Enamorado, C., Ibargüen-González, L., Sánchez-Polo, A., Segura‐Sampedro, J. J., Masmiquel, L., Barceló, C., & González‐Freire, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910547 · Cited by 38
Zhang, K., Sun, W., Huang, L., Zhu, K., Pei, F., Zhu, L., Wang, Q., Lü, Y., Zhang, H., Jin, H., et al. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b08088 · Cited by 35
McCauley, H. A., Riedman, A. M., Enriquez, J. R., Zhang, X., Watanabe‐Chailland, M., Sanchez, J. G., Kechele, D. O., Paul, E. F., Riley, K., Burger, C. A., et al. (2023) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2022.12.016 · Cited by 34
From birth to death: The hardworking life of Paneth cell in the small intestine
Cui, C., Wang, F., Zheng, Y., Wei, H., & Peng, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1122258 · Cited by 37
Time after time: circadian clock regulation of intestinal stem cells
Parasram, K., & Karpowicz, P. A. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03323-x · Cited by 34
Rapamycin Extends Life Span in ApcMin/+ Colon Cancer FAP Model
Parihar, M., Dodds, S. G., Hubbard, G. B., Javors, M. A., Strong, R., Hasty, P., & Sharp, Z. D. (2020) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2020.08.006 · Cited by 35
REGγ drives Lgr5+ stem cells to potentiate radiation induced intestinal regeneration
Zhu, X., Yang, M., Lin, Z., Kibreab, S., Li, Y., Zhang, L., Kong, Y., Zhang, Y., Ren, Y., Li, J., et al. (2021) · Science China Life Sciences · doi:10.1007/s11427-021-2018-7 · Cited by 34
Programmed ageing: decline of stem cell renewal, immunosenescence, and Alzheimer's disease
Lathe, R., & Clair, D. S. (2023) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12959 · Cited by 37
Sun, L., Brown, R. E., Chen, S., Zhuge, Q., & Su, D. (2012) · Aging · doi:10.18632/aging.100487 · Cited by 36
Colorectal cancer initiation: Understanding early-stage disease for intervention
Jiang, C., Zhou, Q., Yi, K., Yuan, Y., & Xie, X. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216831 · Cited by 34
Association of Parkinson’s Disease GWAS-Linked Loci with Alzheimer’s Disease in Han Chinese
Zhu, X., Cao, L., Tan, M., Jiang, T., Wang, H.-F., Lu, H., Tan, C., Zhang, W., Tan, L., & Yu, J. (2016) · Molecular Neurobiology · doi:10.1007/s12035-015-9649-5 · Cited by 34
Diet, Microbiota, and Colorectal Cancer
Grazioso, T. P., Brandt, M., & Djouder, N. (2019) · iScience · doi:10.1016/j.isci.2019.10.011 · Cited by 37
Targeting Mammalian Target of Rapamycin: Prospects for the Treatment of Inflammatory Bowel Diseases
Lashgari, N., Roudsari, N. M., Momtaz, S., Ghanaatian, N., Kohansal, P., Farzaei, M. H., Afshari, K., Sahebkar, A., & Abdolghaffari, A. H. (2020) · Current Medicinal Chemistry · doi:10.2174/0929867327666200504081503 · Cited by 39
The systemic milieu as a mediator of dietary influence on stem cell function during ageing
Murphy, T., & Thuret, S. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.11.004 · Cited by 34
Common alleles that influence autophagy and the risk for inflammatory bowel disease
Gardet, A., & Xavier, R. J. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.08.001 · Cited by 35
Wieck, M. M., Schlieve, C. R., Thornton, M. E., Fowler, K. L., Isani, M. A., Grant, C. N., Hilton, A. E., Hou, X., Grubbs, B. H., Frey, M. R., et al. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.12.008 · Cited by 31
Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids
Zietek, T., Boomgaarden, W., & Rath, E. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13081280 · Cited by 33
Epigenetic Clock and Circadian Rhythms in Stem Cell Aging and Rejuvenation
Samoilova, E. M., Викторович, Б. В., Ekusheva, E. V., Zhang, C., Troitskiy, A. V., & Baklaushev, V. P. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11111050 · Cited by 32
Lopatina, O. L., Furuhara, K., Ishihara, K., Salmina, A. B., & Higashida, H. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00266 · Cited by 30
Intracellular pH dynamics regulates intestinal stem cell lineage specification
Liu, Y., Reyes, E. A., Castillo‐Azofeifa, D., Klein, O. D., Nystul, T. G., & Barber, D. L. (2023) · Nature Communications · doi:10.1038/s41467-023-39312-9 · Cited by 30
Expression of CD24, a Stem Cell Marker, in Pancreatic and Small Intestinal Neuroendocrine Tumors
Salaria, S. N., Means, A. L., Revetta, F. L., Idrees, K., Liu, E. V., & Shi, C. (2015) · American Journal of Clinical Pathology · doi:10.1309/ajcpmzy5p9twnjjv · Cited by 30
Age-related dysfunction of the DNA damage response in intestinal stem cells
Watanabe, K., Ikuno, Y., Kakeya, Y., Ikeno, S., Taniura, H., Kurono, M., Minemori, K., Katsuyama, Y., & Naka-Kaneda, H. (2019) · Inflammation and Regeneration · doi:10.1186/s41232-019-0096-y · Cited by 30
Spheres of Influence: Insights into Salmonella Pathogenesis from Intestinal Organoids
Verma, S., Senger, S., Cherayil, B. J., & Faherty, C. S. (2020) · Microorganisms · doi:10.3390/microorganisms8040504 · Cited by 30
Challenges in Studying Stem Cell Metabolism
Perez-Ramirez, C. A., & Christofk, H. R. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.02.016 · Cited by 30
Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation
Silva, J., Alkan, F., Ramalho, S., Snieckute, G., Preković, S., García, A. K., Hernández-Pérez, S., van der Kammen, R., Barnum, D., Hoekman, L., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32220-4 · Cited by 31
Therapeutic potential of mTOR inhibitors for targeting cancer stem cells
Francipane, M. G., & Lagasse, E. (2015) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12844 · Cited by 31
A nutrient-sensitive restriction point is active during retinal progenitor cell differentiation
Love, N. K., Keshavan, N., Lewis, R., Harris, W. A., & Agathocleous, M. (2014) · Development · doi:10.1242/dev.103978 · Cited by 30
Role of DNA methylation in the dietary restriction mediated cellular memory
Unnikrishnan, A., Jackson, J. A., Matyi, S. A., Hadad, N., Wronowski, B., Georgescu, C., Garrett, K. P., Wren, J. D., Freeman, W. M., & Richardson, A. G. (2017) · GeroScience · doi:10.1007/s11357-017-9976-8 · Cited by 29
Melnik, B. C., & Schmitz, G. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101270 · Cited by 29
A pre-steady state and steady state kinetic analysis of the N-ribosyl hydrolase activity of hCD157
Preugschat, F., Carter, L. H., Boros, E. E., Porter, D. J. T., Stewart, E. L., & Shewchuk, L. M. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.09.008 · Cited by 29
Stem cell mitochondria during aging
Min‐Wen, J. C., Jun‐Hao, E. T., & Shyh‐Chang, N. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.02.005 · Cited by 28
Liu, Z., Xie, W.-W., Zan, G.-X., Gao, C., Yan, H., Zhou, J., & Wang, X. (2021) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2021.109640 · Cited by 28
From 3D Organoids back to 2D Enteroids
Braverman, J., & Yilmaz, Ö. H. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.02.016 · Cited by 28
Self-citationGenetic and epigenetic alterations in aging and rejuvenation of human
Park, K., Jeon, M. C., Lee, D., Kim, J., & Im, S.-W. (2024) · Molecules and Cells · doi:10.1016/j.mocell.2024.100137 · Cited by 30
Roy, E., Neufeld, Z., Livet, J., & Khosrotehrani, K. (2014) · Stem Cells · doi:10.1002/stem.1804 · Cited by 26
Schleit, J., Wasko, B. M., & Kaeberlein, M. R. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.07.038 · Cited by 27
Latest advances in aging research and drug discovery
Bakula, D., Ablasser, A., Aguzzi, A., Antebi, A., Barzilai, N., Bittner, M.-I., Jensen, M. B., Calkhoven, C. F., Chen, D., de Grey, A. D. N. J., et al. (2019) · Aging · doi:10.18632/aging.102487 · Cited by 27
Self-citationDominguez‐Brauer, C., Hao, Z., Elia, A., Fortin, J., Nechanitzky, R., Brauer, P. M., Sheng, Y., Mana, M., Chio, I. I. C., Haight, J., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.04.002 · Cited by 28
Self-citationPaneth Cells: Dispensable yet Irreplaceable for the Intestinal Stem Cell Niche
Quintero, M. K., & Samuelson, L. C. (2024) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2024.101443 · Cited by 27
Energy Metabolism and Metabolic Sensors in Stem Cells: The Metabostem Crossroads of Aging and Cancer
Menéndez, J. A., & Joven, J. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-07320-0_10 · Cited by 27
Engineered Glycocalyx Regulates Stem Cell Proliferation in Murine Crypt Organoids
Rouhanifard, S. H., Aguilar, A. L., Meng, L., Moremen, K. W., & Wu, P. (2018) · Cell chemical biology · doi:10.1016/j.chembiol.2018.01.010 · Cited by 26
Regulation of intestinal growth in response to variations in energy supply and demand
Nilaweera, K. N., & Speakman, J. R. (2018) · Obesity Reviews · doi:10.1111/obr.12780 · Cited by 26
Eskiocak, O., Gewolb, J., Shah, V., Rouse, J. A., Chowdhury, S., Akyildiz, E. O., Fernández-Maestre, I., Boyer, J. A., Filliol, A. A., Harris, A. S., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-01022-w · Cited by 27
Caloric restriction and aging stem cells: The stick and the carrot?
Mazzoccoli, G., Tevy, M. F., Borghesan, M., Vergini, M. R. D., & Vinciguerra, M. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.10.014 · Cited by 28
The intricate connection between diet, microbiota, and cancer: A jigsaw puzzle
Arkan, M. C. (2017) · Seminars in Immunology · doi:10.1016/j.smim.2017.08.009 · Cited by 25
Choi, C., Lee, C., Shin, S.-W., Kim, S., Hong, S. N., & Park, H. C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081894 · Cited by 25
Kong, X., Wang, X., Qin, Y., & Han, J. (2020) · Journal of Applied Toxicology · doi:10.1002/jat.4080 · Cited by 25
Function and treatment strategies of β-hydroxybutyrate in aging
Xiang, Y., Wang, Q., Lan, X., Zhang, H., & Wei, D. (2022) · Smart Materials in Medicine · doi:10.1016/j.smaim.2022.09.003 · Cited by 26
Cables1is a tumor suppressor gene that regulates intestinal tumor progression inApcMinmice
Arnason, T., Pino, M. S., Yilmaz, Ö. H., Kirley, S. D., Rueda, B. R., Chung, D. C., & Zukerberg, L. R. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.25089 · Cited by 25
Self-citationBody mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status
Hanyuda, A., Cao, Y., Hamada, T., Nowak, J. A., Qian, Z. R., Masugi, Y., da Silva, A., Liu, L., Kosumi, K., Soong, T. R., et al. (2017) · European Journal of Epidemiology · doi:10.1007/s10654-017-0254-y · Cited by 25
Mattila, J., Viitanen, A., Fabris, G., Strutynska, T. R., Korzelius, J., & Hietakangas, V. (2024) · Science Advances · doi:10.1126/sciadv.adi2671 · Cited by 26
Fetal-like reversion in the regenerating intestine is regulated by mesenchymal asporin
Iqbal, S., Andersson, S., Nesta, E., Pentinmikko, N., Kumar, A. A., Jha, S. K., Borshagovski, D., Webb, A., Gebert, N., Viitala, E. W., et al. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.02.009 · Cited by 34
Self-citationGrowth of the maternal intestine during reproduction
Ameku, T., Laddach, A., Beckwith, H., Milona, A., Rogers, L. S., Schwayer, C., Nye, E. L., Tough, I. R., Thoumas, J., Gautam, U. K., et al. (2025) · Cell · doi:10.1016/j.cell.2025.02.015 · Cited by 24
Malijauskaite, S., Connolly, S. A., Newport, D. T., & McGourty, K. (2021) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2021.03.002 · Cited by 24
Sarkar, A., Jin, Y., DeFelice, B. C., Logan, C. Y., Yang, Y., Anbarchian, T., Wu, P. V., Morri, M., Neff, N. F., Nguyen, H., et al. (2022) · eLife · doi:10.7554/elife.82311 · Cited by 23
Molecular mechanism of extrinsic factors affecting anti-aging of stem cells
Wong, T. (2015) · World Journal of Stem Cells · doi:10.4252/wjsc.v7.i2.512 · Cited by 24
Characterization of radioresistant epithelial stem cell heterogeneity in the damaged mouse intestine
Sato, T., Sase, M., Ishikawa, S., Kajita, M., Asano, J., Sato, T., Mori, Y., & Ohteki, T. (2020) · Scientific Reports · doi:10.1038/s41598-020-64987-1 · Cited by 24
The unexpected role of mTORC1 in intestinal stem cells during calorie restriction
Igarashi, M., & Guarente, L. (2016) · Cell Cycle · doi:10.1080/15384101.2016.1221210 · Cited by 22
GI stem cells – new insights into roles in physiology and pathophysiology
Henning, S., & von Furstenberg, R. J. (2016) · The Journal of Physiology · doi:10.1113/jp271663 · Cited by 22
The intestinal epithelial response to damage
Weichselbaum, L., & Klein, O. D. (2018) · Science China Life Sciences · doi:10.1007/s11427-018-9331-y · Cited by 22
Gnoni, M. L., Beas, R., & Vásquez-Garagatti, R. (2021) · VirusDisease · doi:10.1007/s13337-021-00703-5 · Cited by 23
Cullin 4b Complex Targets IRGM1 to Regulate Intestinal Stem Cell Stemness and Niche
Fan, Y., Huo, X., Guo, B., Zhang, X., Yang, Y., Lian, J., Meng, X., Shao, Y., Zou, Y., Guo, H., et al. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-022-00954-9 · Cited by 21
Cell plasticity in regeneration in the stomach and beyond
Adkins-Threats, M., & Mills, J. C. (2022) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2022.101948 · Cited by 23
Key regulators of intestinal stem cells: diet, microbiota, and microbial metabolites
Yao, C., Gou, X., Tian, C., Zhou, L., Hao, R., Li, W., Wang, Z., Li, M., & Tong, X. (2022) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2022.12.002 · Cited by 25
Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate
Oichi, T., Kodama, J., Wilson, K., Tian, H., Kawasawa, Y. I., Usami, Y., Oshima, Y., Saito, T., Tanaka, S., Iwamoto, M., et al. (2023) · Bone Research · doi:10.1038/s41413-023-00258-9 · Cited by 22
The mTOR signalling in corneal diseases: A recent update
Li, X., Chen, K., Wang, Z., Li, J., Wang, X., Xie, C., Tong, J., & Shen, Y. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115620 · Cited by 24
Intestinal stem cells and celiac disease
Piscaglia, A. C. (2014) · World Journal of Stem Cells · doi:10.4252/wjsc.v6.i2.213 · Cited by 22
Dietary cysteine enhances intestinal stemness via CD8+ T cell-derived IL-22
Chi, F., Zhang, Q., Shay, J. E. S., Han, S., ten Hoeve, J., Yuan, Y., Yang, Z., Shin, H., Block, S., Solanki, S. A., et al. (2025) · Nature · doi:10.1038/s41586-025-09589-5 · Cited by 23
Self-citationPaneth cells in farm animals: current status and future direction
Cui, C., Li, L., Wu, L., Wang, X., Zheng, Y., Wang, F., Wei, H., & Peng, J. (2023) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-023-00905-5 · Cited by 20
An enduring role for quiescent stem cells
Richmond, C. A., Shah, M. S., Carlone, D. L., & Breault, D. T. (2016) · Developmental Dynamics · doi:10.1002/dvdy.24416 · Cited by 23
Gutiérrez‐Repiso, C., García‐Serrano, S., Moreno‐Ruiz, F. J., Alcaín‐Martínez, G., Rodríguez‐Pacheco, F., & García‐Fuentes, E. (2016) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2016.11.021 · Cited by 23
Obesity and intestinal stem cell susceptibility to carcinogenesis
Pourvali, K., & Monji, H. (2021) · Nutrition & Metabolism · doi:10.1186/s12986-021-00567-y · Cited by 22
Sundaram, S., & Borthakur, A. (2021) · Biochemical Journal · doi:10.1042/bcj20200902 · Cited by 21
Nutrient metabolism in regulating intestinal stem cell homeostasis
Shi, R., & Wang, B. (2024) · Cell Proliferation · doi:10.1111/cpr.13602 · Cited by 19
Intestinal Stem Cell Niche Insights Gathered from BothIn Vivoand NovelIn VitroModels
Gjorevski, N., & Ordóñez‐Morán, P. (2017) · Stem Cells International · doi:10.1155/2017/8387297 · Cited by 21
Resemblance and differences in dietary restriction nephroprotective mechanisms in young and old rats
Andrianova, N. V., Zorova, L. D., Pevzner, I. B., Popkov, V. A., Chernikov, V. P., Silachev, D. N., Plotnikov, E. Y., & Zorov, D. B. (2020) · Aging · doi:10.18632/aging.103960 · Cited by 20
Tsai, R. Y. L. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2152-y · Cited by 20
NOD2 Supports Crypt Survival and Epithelial Regeneration after Radiation-Induced Injury
Lee, C., Choi, C., Kang, H. S., Shin, S.-W., Kim, S., Park, H. C., & Hong, S. N. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20174297 · Cited by 20
Metabolic regulation of intestinal homeostasis: molecular and cellular mechanisms and diseases
Zhang, R., Perekatt, A. O., & Chen, L. (2024) · MedComm · doi:10.1002/mco2.776 · Cited by 21
Wang, D., Li, P., Odle, J., Lin, X., Zhao, J., Xiao, K., & Liu, Y. (2021) · Nutrition Research Reviews · doi:10.1017/s0954422421000172 · Cited by 20
Metadata
- Authors
- Yilmaz, Ö. H., Katajisto, P., Lamming, D. W., Gültekin, Y., Bauer-Rowe, K. E., Sengupta, S., Birsoy, K., Dursun, A., Yilmaz, V. O., Selig, M., Nielsen, G. P., Mino-Kenudson, M., Zukerberg, L. R., Bhan, A. K., Deshpande, V., & Sabatini, D. M.
- Affiliations
- Harvard University (US)
- Broad Institute (US)
- Corresponding author
- Sabatini, David M.
- ORCID
- Venue
- Nature
- Published
- 2012-05-20
- Volume
- 486
- Issue
- 7404
- Pages
- 490-495
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3387287
- OpenAlex
- W2113486346
- Cited by
- 753
- References
- 33
- Citations by year
- 2026: 38 · 2025: 45 · 2024: 44 · 2023: 58 · 2022: 53 · 2021: 75 · 2020: 69 · 2019: 54 · 2018: 63 · 2017: 56 · 2016: 39 · 2015: 39 · 2014: 52 · 2013: 47 · 2012: 19
- FWCI
- 20.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (F32AG032833)
- National Cancer Institute (T32CA09216, CA129105, CA103866, R01CA103866, R01CA129105, T32CA009216)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mTORC1, Paneth cells, intestinal stem cells, intestinal stem cell niche, caloric restriction, BST1, cyclic ADP-ribose, paracrine signaling, stem cell self-renewal, intestinal regeneration, nutritional status, rapamycin, lifespan
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Energy Intake, Cell Count, Cell Division, Female, Intestines, Longevity, Male, Proteins, Regeneration, Stem Cells, Signal Transduction, Antigens, CD, Paneth Cells, Paracrine Communication, Sirolimus, Caloric Restriction, ADP-ribosyl Cyclase, Cyclic ADP-Ribose, Multiprotein Complexes, Mice, Stem Cell Niche, TOR Serine-Threonine Kinases, GPI-Linked Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
